Variant rs10509688 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002860.4(ALDH18A1):c.1153-30T>C variant causes a intron change. The variant allele was found at a frequency of 0.166 in 1,582,184 control chromosomes in the GnomAD database, including 24,766 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2023 hom., cov: 30)

Exomes 𝑓: 0.17 ( 22743 hom. )

Consequence

ALDH18A1
NM_002860.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.69

Variant links:

Genes affected

ALDH18A1 (HGNC:9722): (aldehyde dehydrogenase 18 family member A1) This gene is a member of the aldehyde dehydrogenase family and encodes a bifunctional ATP- and NADPH-dependent mitochondrial enzyme with both gamma-glutamyl kinase and gamma-glutamyl phosphate reductase activities. The encoded protein catalyzes the reduction of glutamate to delta1-pyrroline-5-carboxylate, a critical step in the de novo biosynthesis of proline, ornithine and arginine. Mutations in this gene lead to hyperammonemia, hypoornithinemia, hypocitrullinemia, hypoargininemia and hypoprolinemia and may be associated with neurodegeneration, cataracts and connective tissue diseases. Alternatively spliced transcript variants, encoding different isoforms, have been described for this gene. [provided by RefSeq, Jul 2008]

ALDH18A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-95625485-A-G is Benign according to our data. Variant chr10-95625485-A-G is described in ClinVar as [Benign]. Clinvar id is 258824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH18A1	NM_002860.4 linkuse as main transcript	c.1153-30T>C		intron_variant		ENST00000371224.7	NP_002851.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ALDH18A1	ENST00000371224.7 linkuse as main transcript	c.1153-30T>C	intron_variant	1	NM_002860.4	ENSP00000360268	P3	P54886-1
ALDH18A1	ENST00000371221.3 linkuse as main transcript	c.1147-30T>C	intron_variant	1		ENSP00000360265	A1	P54886-2
ALDH18A1	ENST00000489386.1 linkuse as main transcript	n.518-30T>C	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21845

AN:

151832

Hom.:

2011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0748

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.486

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.175

AC:

43908

AN:

250610

Hom.:

4976

AF XY:

0.176

AC XY:

23819

AN XY:

135478

show subpopulations

Gnomad AFR exome

AF:

0.0729

Gnomad AMR exome

AF:

0.114

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.491

Gnomad SAS exome

AF:

0.159

Gnomad FIN exome

AF:

0.188

Gnomad NFE exome

AF:

0.165

Gnomad OTH exome

AF:

0.163

GnomAD4 exome

AF:

0.169

AC:

241273

AN:

1430234

Hom.:

22743

Cov.:

AF XY:

0.168

AC XY:

119967

AN XY:

713658

show subpopulations

Gnomad4 AFR exome

AF:

0.0666

Gnomad4 AMR exome

AF:

0.114

Gnomad4 ASJ exome

AF:

0.122

Gnomad4 EAS exome

AF:

0.468

Gnomad4 SAS exome

AF:

0.161

Gnomad4 FIN exome

AF:

0.191

Gnomad4 NFE exome

AF:

0.164

Gnomad4 OTH exome

AF:

0.164

GnomAD4 genome

AF:

0.144

AC:

21888

AN:

151950

Hom.:

2023

Cov.:

AF XY:

0.144

AC XY:

10708

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.0751

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.117

Gnomad4 EAS

AF:

0.486

Gnomad4 SAS

AF:

0.156

Gnomad4 FIN

AF:

0.179

Gnomad4 NFE

AF:

0.162

Gnomad4 OTH

AF:

0.134

Alfa

AF:

0.157

Hom.:

4272

Bravo

AF:

0.139

Asia WGS

AF:

0.323

AC:

1120

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over